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Editorial : An uncalculated risk – Does a chance of disaster mean we should ignore an opportunity to save lives?

A PIONEERING operation promises to save thousands of lives now and many
more in the future. But it could also unleash a new and deadly plague. The
benefits from the treatment are obvious and immediate, the risks unknown and so
far impossible to estimate.

What do you do? Press on optimistically on the grounds that there would be no
progress if everyone worried about every possible risk? Or take the pessimistic
view that too many of the world’s problems have been caused because people saw
the immediate gains but not the long-term problems? Usually, the optimists win
the day. And despite a few little headaches—like the Chernobyl
accident—the nightmare scenarios envisaged by the pessimists do not come
to pass.

Xenotransplantation—the transplantation of body parts from one species
into another—is hurtling along the optimists’ route. But there are good
reasons for thinking that the brakes should be applied, not to bring progress to
a complete halt as some pessimists are demanding, but in order to proceed with
more caution.

There is tremendous pressure to hurry xenotransplantation along. The demand
for human organs has vastly outgrown the supply. Already, around half of all
people who need a transplant die while still on the waiting list. And there is
not much prospect of increasing the supply. Organs need to come from healthy
bodies, but fewer young people are dying in accidents.

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Animal organs seem to be the only solution and pigs the best bet. They are
roughly the same size as humans and we already breed them in large numbers. And
there has been rapid progress in genetically engineering pigs so that their
organs are less likely to be rejected by a human body.

So far, so good. Unfortunately, there is also a risk. All animals harbour
viruses and placing an organ from another species inside you is the perfect way
for those viruses to jump the species barrier. The AIDS epidemic probably began
when HIV crossed from monkeys to humans. HTLV, which causes leukaemia, is
another virus that crossed the species barrier, as did those causing Marburg
disease and Lassa fever. It’s a pretty nasty list to which you can add various
strains of influenza.

The big question is whether xenotransplants will be followed by epidemics of
viruses new to humans. Researchers have been hoping to get around this risk by
breeding pigs completely free of the viruses that could grow in humans. But the
latest evidence suggests that this will not be possible(see p 4). All pig cells
appear to contain multiple copies of retroviruses that can infect human cells.
And as the viruses are integrated into the pig’s DNA, breeding them out is
likely to be impossible.

This is not to say that xenotransplantation should be banned. The risks are
unknown and there is little chance of a blanket ban anyway—experiments
using pig livers are already beginning in the US. But we can ask that the use of
xenotransplantation be delayed while better ways are found of assessing and
monitoring the risk.

Regulations in the US and Britain already demand that xenotransplantation
patients are subject to lifetime surveillance. The problem is that no one has
worked out how that surveillance should be carried out or what to make of any
data gathered. We lack inventories of pig viruses and knowledge of how
infectious the viruses are likely to be. Even if we followed a patient with a
pig’s liver and found pig retroviruses in blood tests we would not know for sure
whether an infection was spreading or pig cells had simply escaped into the
bloodstream.

Before taking the next step, we need to be certain that our surveillance
methods are likely to be successful. The methods can be tested in pig-to-primate
transplants. Some experiments have already begun and the results must be
examined before we rush headlong into xenotransplant operations.

With reliable follow-up, we could at least feel that we had a chance of
catching problems early on. Should something go seriously wrong the alternatives
are too horrible to contemplate: at worst a new epidemic or, at best, state
control of those carrying a new communicable disease. Imagine if pigs’ livers
saved lives but condemned those receiving them to life in a remote sanatorium.
It is a scenario far too reminiscent of an old horror movie.